支链氨基酸对多囊卵巢综合征代谢与生殖的影响

doi:10.12280/gjszjk.20220391

摘要/Abstract

摘要：

多囊卵巢综合征（polycystic ovary syndrome，PCOS）是育龄期女性常见的生殖内分泌疾病，患者常伴有胰岛素抵抗、肥胖、不孕及不良妊娠结局等临床表现，严重影响女性身心健康。近年研究表明，支链氨基酸（branched-chain amino acid，BCAA）在PCOS患者体内存在代谢异常，并且可能作为标志物预测PCOS相关并发症的发生风险。BCAA作为人体的必需氨基酸，通过多种途径参与胰岛素的调节、调控脂肪的生成与分化，对维持机体稳态具有重要作用，同时其水平变化可能会影响女性的生殖功能。PCOS患者循环中BCAA过高可导致糖脂代谢紊乱，促进胰岛素抵抗和肥胖的发生，也可对育龄期患者排卵及妊娠造成不利影响。综述BCAA在PCOS糖脂代谢和生殖方面的作用及研究进展，以期为PCOS代谢与生殖方面疾病的诊治提供新思路。

关键词: 氨基酸类，支链, 多囊卵巢综合征, 胰岛素抗药性, 肥胖症, 生殖

Abstract:

Polycystic ovary syndrome(PCOS) is a common reproductive endocrine disease in women of childbearing age. Patients are often accompanied by clinical manifestations such as insulin resistance, obesity, infertility and poor pregnancy outcome, which seriously affect women′s physical and mental health. Recent studies have shown that some patients with PCOS have the metabolic abnormality of branched-chain amino acids (BCAA), and that BCAA may be used as a marker to predict the risk of PCOS related complications. As an essential amino acid of human body, BCAA plays an important role in maintaining the homeostasis of the body by participating in the regulation of insulin secretion, and fat generation and differentiation. The change of BCAA level will affect the reproductive function of women. In addition, the excessive level of serum BCAA in PCOS patients is related to the disorders of glucose and lipid metabolism, the insulin resistance and obesity, and the adverse effect on ovulation and pregnancy in those patients of childbearing age. In this paper, the roles of BCAA in the metabolism of glucose and lipid and reproduction, as well as research progress, were reviewed, so as to provide new ideas for the diagnosis and treatment of metabolic and reproductive diseases in PCOS patients.

Key words: Amino acids, branched-chain, Polycystic ovary syndrome, Insulin resistance, Obesity, Reproduction

冯晓玲, 陈瑶, 王颖. 支链氨基酸对多囊卵巢综合征代谢与生殖的影响[J]. 国际生殖健康/计划生育杂志, 2023, 42(1): 72-76.

FENG Xiao-ling, CHEN Yao, WANG Ying. Effects of Branched-Chain Amino Acids on Metabolism and Reproduction in Polycystic Ovary Syndrome[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(1): 72-76.

参考文献 34

[1]	马帅, 张蓓, 李媛. 多囊卵巢综合征诊断标准的变迁[J]. 中国计划生育和妇产科, 2020, 12(2):6-9. doi: 10.3969/j.issn.1674-4020.2020.02.03. doi: 10.3969/j.issn.1674-4020.2020.02.03
[2]	程天缘, 王昕. 多囊卵巢综合征合并糖脂代谢异常中西医研究进展[J]. 辽宁中医药大学学报, 2022, 24(3):73-78. doi: 10.13194/j.issn.1673-842x.2022.03.016. doi: 10.13194/j.issn.1673-842x.2022.03.016
[3]	Rahat H, Garcia-Reyes Y, Pyle L, et al. The branched-chain amino acid valine is higher and relates to insulin sensitivity in polycystic ovary syndrome[J]. J Inv Med, 2018, 66(1):71-72. doi: 10.1136/jim-2017-000663.23. doi: 10.1136/jim-2017-000663.23
[4]	Tang L, Yuan L, Yang G, et al. Changes in whole metabolites after exenatide treatment in overweight/obese polycystic ovary syndrome patients[J]. Clin Endocrinol(Oxf), 2019, 91(4):508-516. doi: 10.1111/cen.14056. doi: 10.1111/cen.14056 URL
[5]	Szmygin H, Lenart-Lipinska M, Szydelko J, et al. Branched-chain amino acids as a novel biomarker of metabolic disturbances in women with polycystic ovary syndrome-literature review[J]. Ginekol Pol, 2022, 93(8):665-669. doi: 10.5603/GP.a2022.0079. doi: 10.5603/GP.a2022.0079 pmid: 35942720
[6]	Zhang CM, Zhao Y, Li R, et al. Metabolic heterogeneity of follicular amino acids in polycystic ovary syndrome is affected by obesity and related to pregnancy outcome[J]. BMC Pregnancy Childbirth, 2014, 14:11. doi: 10.1186/1471-2393-14-11. doi: 10.1186/1471-2393-14-11 URL
[7]	Manta-Vogli PD, Schulpis KH, Dotsikas Y, et al. The significant role of amino acids during pregnancy: nutritional support[J]. J Matern Fetal Neonatal Med, 2020, 33(2):334-340. doi: 10.1080/14767058.2018.1489795. doi: 10.1080/14767058.2018.1489795 pmid: 29909700
[8]	Neinast M, Murashige D, Arany Z. Branched Chain Amino Acids[J]. Annu Rev Physiol, 2019, 81:139-164. doi: 10.1146/annurev-physiol-020518-114455. doi: 10.1146/annurev-physiol-020518-114455 pmid: 30485760
[9]	李双玲, 王志华. 支链氨基酸代谢在心血管疾病中作用的研究进展[J]. 广西医学, 2021, 43(18):2235-2238. doi: 10.11675/j.issn.0253-4304.2021.18.18. doi: 10.11675/j.issn.0253-4304.2021.18.18
[10]	Neinast MD, Jang C, Hui S, et al. Quantitative Analysis of the Whole-Body Metabolic Fate of Branched-Chain Amino Acids[J]. Cell Metab, 2019, 29(2):417-429.e4. doi: 10.1016/j.cmet.2018.10.013. doi: S1550-4131(18)30645-4 pmid: 30449684
[11]	杨文慧, 何燕, 杨莉. 支链氨基酸代谢与胰岛素抵抗及2型糖尿病研究进展[J]. 中华老年心脑血管病杂志, 2019, 21(4):434-436. doi: 10.3969/j.issn.1009-0126.2019.04.025. doi: 10.3969/j.issn.1009-0126.2019.04.025
[12]	Yoon MS. The Emerging Role of Branched-Chain Amino Acids in Insulin Resistance and Metabolism[J]. Nutrients, 2016, 8(7):405. doi: 10.3390/nu8070405. doi: 10.3390/nu8070405 URL
[13]	Calvo IA, Sharma S, Paulo JA, et al. The fission yeast FLCN/FNIP complex augments TORC1 repression or activation in response to amino acid (AA) availability[J]. iScience, 2021, 24(11):103338. doi: 10.1016/j.isci.2021.103338. doi: 10.1016/j.isci.2021.103338 URL
[14]	陈嘉艺, 周昕博, 单安山, 等. 支链氨基酸对动物糖脂代谢的调控及作用机理[J]. 动物营养学报, 2020, 32(9):4078-4085. doi: 10.3969/j.issn.1006-267x.2020.09.015. doi: 10.3969/j.issn.1006-267x.2020.09.015
[15]	White PJ, McGarrah RW, Grimsrud PA, et al. The BCKDH Kinase and Phosphatase Integrate BCAA and Lipid Metabolism via Regulation of ATP-Citrate Lyase[J]. Cell Metab, 2018, 27(6):1281-1293.e7. doi: 10.1016/j.cmet.2018.04.015. doi: S1550-4131(18)30258-4 pmid: 29779826
[16]	郭一帆, 陈佩杰, 肖卫华. 肥胖状态下脂肪组织线粒体功能紊乱与运动调控[J]. 中国生物化学与分子生物学报, 2020, 36(10):1145-1150. doi: 10.13865/j.cnki.cjbmb.2020.08.1196. doi: 10.13865/j.cnki.cjbmb.2020.08.1196
[17]	马清泉, 王国红, 周昕博, 等. 亮氨酸和异亮氨酸对脂肪沉积的影响及机制[J]. 东北农业大学学报, 2020, 51(1):50-56,64. doi: 10.19720/j.cnki.issn.1005-9369.2020.01.006. doi: 10.19720/j.cnki.issn.1005-9369.2020.01.006
[18]	Zhao Y, Fu L, Li R, et al. Metabolic profiles characterizing different phenotypes of polycystic ovary syndrome: plasma metabolomics analysis[J]. BMC Med, 2012, 10:153. doi: 10.1186/1741-7015-10-153. doi: 10.1186/1741-7015-10-153 pmid: 23198915
[19]	Siddik MAB, Shin AC. Recent Progress on Branched-Chain Amino Acids in Obesity, Diabetes, and Beyond[J]. Endocrinol Metab(Seoul), 2019, 34:234-246. doi: 10.3803/EnM.2019.34.3.234. doi: 10.3803/EnM.2019.34.3.234
[20]	孙旭, 赖建强, 王杰. 支链氨基酸与妊娠期糖尿病关系及作用机制[J]. 卫生研究, 2021, 50(2):337-341. doi: 10.19813/j.cnki.weishengyanjiu.2021.02.031. doi: 10.19813/j.cnki.weishengyanjiu.2021.02.031
[21]	Newgard CB, An J, Bain JR, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance[J]. Cell Metab, 2009, 9(4):311-326. doi: 10.1016/j.cmet.2009.02.002. doi: 10.1016/j.cmet.2009.02.002 pmid: 19356713
[22]	Newgard CB. Interplay between lipids and branched-chain amino acids in development of insulin resistance[J]. Cell Metab, 2012, 15(5):606-614. doi: 10.1016/j.cmet.2012.01.024. doi: 10.1016/j.cmet.2012.01.024 pmid: 22560213
[23]	Asghari G, Farhadnejad H, Teymoori F, et al. High dietary intake of branched-chain amino acids is associated with an increased risk of insulin resistance in adults[J]. J Diabetes, 2018, 10(5):357-364. doi: 10.1111/1753-0407.12639. doi: 10.1111/1753-0407.12639 pmid: 29281182
[24]	Yu D, Richardson NE, Green CL, et al. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine[J]. Cell Metab, 2021, 33(5):905-922.e6. doi: 10.1016/j.cmet.2021.03.025. doi: 10.1016/j.cmet.2021.03.025 pmid: 33887198
[25]	杨珺兰, 王泽, 邹晓燕, 等. PCOS肥胖脂代谢特点及相关基因研究进展[J]. 现代妇产科进展, 2022, 31(5):377-379,383. doi: 10.13283/j.cnki.xdfckjz.2022.05.014. doi: 10.13283/j.cnki.xdfckjz.2022.05.014
[26]	Serralde-Zúñiga AE, Guevara-Cruz M, Tovar AR, et al. Omental adipose tissue gene expression, gene variants, branched-chain amino acids, and their relationship with metabolic syndrome and insulin resistance in humans[J]. Genes Nutr, 2014, 9(6):431. doi: 10.1007/s12263-014-0431-5. doi: 10.1007/s12263-014-0431-5 pmid: 25260659
[27]	Hajitarkhani S, Moini A, Hafezi M, et al. Differences in gene expression of enzymes involved in branched-chain amino acid metabolism of abdominal subcutaneous adipose tissue between pregnant women with and without PCOS[J]. Taiwan J Obstet Gynecol, 2021, 60(2):290-294. doi: 10.1016/j.tjog.2020.12.008. doi: 10.1016/j.tjog.2020.12.008 pmid: 33678329
[28]	White PJ, Lapworth AL, An J, et al. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export[J]. Mol Metab, 2016, 5(7):538-551. doi: 10.1016/j.molmet.2016.04.006. doi: S2212-8778(16)30030-8 pmid: 27408778
[29]	李晓敏, 黄文洁, 卢永超. 多囊卵巢综合征排卵障碍的发生机制[J]. 中国医药导刊, 2021, 23(7):486-490. doi: 10.3969/j.issn.1009-0959.2021.07.003. doi: 10.3969/j.issn.1009-0959.2021.07.003
[30]	梁宝珠, 钟春华, 李彩娟, 等. 多囊卵巢综合征所致复发性流产与体重指数、胰岛素抵抗及疗效相关性研究[J]. 中国优生与遗传杂志, 2015, 23(4):77-79.
[31]	Xu J, Wang J, Cao Y, et al. Downregulation of Placental Amino Acid Transporter Expression and mTORC1 Signaling Activity Contributes to Fetal Growth Retardation in Diabetic Rats[J]. Int J Mol Sci, 2020, 21(5):1849. doi: 10.3390/ijms21051849. doi: 10.3390/ijms21051849 URL
[32]	刘学思, 乔岩岩. 多囊卵巢综合征患者自然流产发病机制的研究进展[J]. 中国优生与遗传杂志, 2021, 29(7):1034-1039.
[33]	Bartolacci A, Buratini J, Moutier C, et al. Maternal body mass index affects embryo morphokinetics: a time-lapse study[J]. J Assist Reprod Genet, 2019, 36(6):1109-1116. doi: 10.1007/s10815-019-01456-3. doi: 10.1007/s10815-019-01456-3 URL
[34]	Chang AY, Lalia AZ, Jenkins GD, et al. Combining a nontargeted and targeted metabolomics approach to identify metabolic pathways significantly altered in polycystic ovary syndrome[J]. Metabolism, 2017, 71:52-63. doi: 10.1016/j.metabol.2017.03.002. doi: 10.1016/j.metabol.2017.03.002 URL